Primary sensory neurons transmit painful and non-painful thermal and mechanical stimuli from the periphery to the spinal cord. Physiological studies have identified a number of functionally distinct subtypes of primary sensory neurons (defined by their response to stimuli, degree of myelination and innervation pattern), but how each type contributes to behavior is still not well understood. The identification of molecular markers for each population is now permitting the use of more powerful genetic approaches to identify functionally important molecules, map their central connectivity and determine their role in somatosensory perception. In this grant proposal, we take advantage of a unique molecular marker we identified and these new powerful tools to elucidate the central circuitry activated by unmyelinated low threshold mechanoreceptors (C-LTMRs). These cells are thought to transmit pleasant touch and the persistent mechanical pain that results from nerve injury. We will also take advantage of a new transgenic reporter line we developed to identify molecular markers for additional functionally defined primary sensory populations. Marker genes will allow us to address many aspects of somatosensory biology that were previously not feasible. These new approaches are absolutely essential for understanding the fundamental principles of somatosensory processing and its relation to perception under normal conditions and in chronic pain states.